Growth of cells in medium containing serum has been the standard for cell culture for decades. Serum enhances cell adhesion to culture vessels, adhesiveness being a requirement for cell viability in vitro, and provides factors that promote cell growth and function.
Cells are capable of differentiating in vitro in response to specific signals, but the presence of serum in the culture medium often results in loss of differentiative functions, i.e., specific characteristics not found in the immature cell. For example, human myeloid leukemia cells were induced to differentiate by exposure to exogenous serine proteases or to 12-O-tetradecanoylphorbol-13-acetate (Honma et al., 1982, Gann 73: 97), and murine neuroblastoma cells were induced to differentiate in the presence of cAMP effectors (Gibson et al., 1984, J. Cell. Physiol. 119: 119), yet the level of morphological differentiation of these cells in medium containing fetal calf serum or calf serum was found to be significantly lower than in serum-free media. Similarly erythroleukemia cells were induced to differentiate by exposure to dimethylsulfoxide, in the presence of non-mouse serum. When mouse serum was added to the culture, erythroid cell differentiation is inhibited (Parker et al., 1981, Leuk. Res. 5: 123). In addition, hepatocytes were induced to differentiate in culture by, e.g., addition of non-physiologic amounts of glucocorticoid hormones, dimethylsulfoxide, or phenobartitol, but these treatments have been found to alter normal ethanol metabolism or normal amounts and types of microsomal enzymes involved in drug metabolism (Paine et al., 1982, Blochem. Pharmacol. 31: 1175).
Conte and Tasat (1986, J. Steroid Biochem. 24:749) postulated that inhibition of rat epithelial cell differentiation by fetal calf serum may be due to the presence of vitamin A. Lin et al. (1987, Mol. Cell. Biol. 7:4324) identified an inhibitor of glucagon sensitivity in cultured kidney cells as being a fetal bovine serum factor of 50-100 kD.